Respiratory Syncytial Virus (RSV) is an important cause of morbidity and mortality in elderly adults and those with high-risk cardiopulmonary conditions. Among community dwelling elderly and high-risk persons, RSV infections can be documented in 3-10 percent of persons annually and influenza A in 0-5 percent. Among hospitalized persons, RSV accounts for 9.7 percent of admissions for acute respiratory disease in the winter, compared to 12.1 percent for influenza A. The clinical impact of the two viruses is similar. Although the presence of underlying disease and low serum neutralizing antibody titers is correlated with risk of hospitalization, other factors are likely to contribute to disease severity. Results in experimental animal models have convincingly demonstrated that cellular immune responses to RSV are determining factors in lung pathology following infection. Neither the pathogenesis nor the cellular immune response to RSV in elderly persons has been investigated. This research will investigate those factors associated with severe RSV infection in older persons. The primary hypothesis to be tested is that age-associated changes in the RSV-specific cellular immune response during infection lead to impaired clearance of virus and more severe disease in the elderly. The research will be conducted in RSV infected young and old adults with a spectrum of disease severity ranging from mild to severe. Measures of the innate and adaptive cellular and humoral immune response, the genetics of viral clearance, and inflammatory markers will be examined in these persons when they are seen in physician's offices or admitted to the hospital with symptomatic RSV illnesses. The interrelationships between these factors, older age, the presence of underlying diseases, and RSV disease severity will be determined by multivariate analysis. Using this data, the contribution of each factor to disease severity can be estimated. An understanding of disease pathogenesis useful for guiding optimal approaches to novel therapies and in development of vaccines for RSV in this age group. Assessment of viral load and possible spread to the lower airways, as well as the pattern of viral clearance in older adults will be important to better predict whether antivirals or immunomodulators will be useful. Additionally, this information coupled with knowledge of the immune and inflammatory response to infection will better allow us to predict the type of vaccine, adjuvants and delivery systems required to prevent infection and disease.